Positron emission tomography (PET) is a noninvasive and highly sensitive imaging technology for quantitative measurement in the picomolar range and visualization of biological interactions in vivo at the molecular level. Several positron-emitting radioisotopes can be incorporated into biomolecules, but the most prominent radionuclide in the clinic is fluorine-18 (18F). By far [18F]fluorodeoxyglucose ([18F]FDG), the most successful commercial PET radiopharmaceutical, has prevailed in oncological diagnosis over two decades.
However, this molecular imaging modality is far from fully exploited, mainly because chemical reactions to introduce 18F atom into radiotracer candidates are limited. In addition to the difficulty in C—F bond formation, short half-life of 18F (˜110 min), low 18F concentration as well as solvent compatibility exacerbate the development of 18F labeling methodology. Typically, most of radiotracers are labeled through nucleophilic 18F substitution, in which harsh reaction conditions are required and therefore, functional group compatibility is diminished. Recently, a number of novel 18F labeling strategies have been developed that can incorporate 18F into molecules of increasing complexity. Some of these methods have been scaled up and demonstrated in image applications with high specify activity.
Nevertheless, most of current 18F labeling methods follow “preinstallation” strategy, in which a reactive functional group is preinstalled at the proposed labeled site and subsequently substituted by 18F. Additional synthetic steps to prepared reactive precursors and harsh reaction conditions of 18F labeling step limit the application into a broad substrate scope.